We have recently shown that there is a substance (or substances) excreted by the kidneys of laboratory rabbits and human beings which when injected into the laboratory rabbit, or prevented from being excreted (in nephrectomized rabbits or in hemodialysis patients with partial renal function) results in a fall in body temperature and an attenuation of pyrogen-induced fever. We have called this substance(s) "endogenous cryogen" (EC) since it not only is an effective antipyretic but also reduces normal resting body temperature. Several important questions remain to be answered about EC. Exactly how does this substance induce a fall in body temperature? What are the chemical properties of EC? Does EC have a physiological role? The specific aims of this research proposal are to answer the above questions about this newly discovered and potentially important naturally occurring cryogen. These will involve experiments aimed at (a) determining the effects of human urine on the thermal responses (skin, and core temperature, respiratory rate, and oxygen uptake) of rabbits, (b) isolating and identifying EC (e.g., by ultrafiltration, hydrolysing any cryogenic proteins, etc.), and (c) determining whether EC has a physiological role by collecting urine at various times when body temperature is high and low and testing this urine for the concentration of cryogens.